pH-dependent production of himeic acid A and its non-enzymatic conversions to himeic acids B and C

Katsuki, Ayako; Kato, Hikaru; Tahara, Yurika; Hashimoto, Makoto; Fujii, Isao; Tsukamoto, Sachiko

doi:10.1016/j.bmc.2018.02.034

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…In addition to the γ-pyrone ring system, it comprises an unusual unsymmetric acyclic imide, a homochiral 2-methyl succinic acid fragment, as well as an unsaturated C 11 carboxylic acid side-chain. One challenge to the synthesis of 1 is the sensitivity of the imide functionality which is known to undergo cleavage even under treatment with MeOH (∼50% after 5 days) …”

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confidence: 99%

“…One challenge to the synthesis of 1 is the sensitivity of the imide functionality which is known to undergo cleavage even under treatment with MeOH (∼50% after 5 days). 19 Several approaches to the 2,5-disubstituted γ-pyrone core of himeic acid A can be considered. 20 However, after extensive efforts, we focused on a strategy based on the McCombie reaction 21 to form the core γ-pyrone ring system in 1 (Scheme 1).…”

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confidence: 99%

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Total Synthesis of the 2,5-Disubstituted γ-Pyrone E1 UAE Inhibitor Himeic Acid A

Lu,

Handore,

Wood

et al. 2023

Org. Lett.

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The first total synthesis of the E1 ubiquitin-activating enzyme inhibitor, himeic acid A, is reported. A McCombie reaction was used to form the core γ-pyrone via a 6π-electrocyclization. A dioxenone ring-opening/acyl ketene trapping reaction with a primary amide provided the unusual unsymmetrical imide functionality. Other key steps include the use of an Evans auxiliary alkylation (d.r. ≥ 95:5) to install the (S)-2-methyl succinic acid fragment and a cross-metathesis to install the unsaturated side-chain.

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confidence: 99%

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confidence: 99%

Total Synthesis of the 2,5-Disubstituted γ-Pyrone E1 UAE Inhibitor Himeic Acid A

Lu,

Handore,

Wood

et al. 2023

Org. Lett.

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Assembly Line and Post-PKS Modifications in the Biosynthesis of Marine Polyketide Natural Products

Zhang

Yang

et al. 2020

Comprehensive Natural Products III

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Fungal Secondary Metabolites as Inhibitors of the Ubiquitin–Proteasome System

Staszczak

2021

IJMS

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The ubiquitin–proteasome system (UPS) is the major non-lysosomal pathway responsible for regulated degradation of intracellular proteins in eukaryotes. As the principal proteolytic pathway in the cytosol and the nucleus, the UPS serves two main functions: the quality control function (i.e., removal of damaged, misfolded, and functionally incompetent proteins) and a major regulatory function (i.e., targeted degradation of a variety of short-lived regulatory proteins involved in cell cycle control, signal transduction cascades, and regulation of gene expression and metabolic pathways). Aberrations in the UPS are implicated in numerous human pathologies such as cancer, neurodegenerative disorders, autoimmunity, inflammation, or infectious diseases. Therefore, the UPS has become an attractive target for drug discovery and development. For the past two decades, much research has been focused on identifying and developing compounds that target specific components of the UPS. Considerable effort has been devoted to the development of both second-generation proteasome inhibitors and inhibitors of ubiquitinating/deubiquitinating enzymes. With the feature of unique structure and bioactivity, secondary metabolites (natural products) serve as the lead compounds in the development of new therapeutic drugs. This review, for the first time, summarizes fungal secondary metabolites found to act as inhibitors of the UPS components.

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pH-dependent production of himeic acid A and its non-enzymatic conversions to himeic acids B and C

Cited by 3 publications

References 17 publications

Total Synthesis of the 2,5-Disubstituted γ-Pyrone E1 UAE Inhibitor Himeic Acid A

Total Synthesis of the 2,5-Disubstituted γ-Pyrone E1 UAE Inhibitor Himeic Acid A

Assembly Line and Post-PKS Modifications in the Biosynthesis of Marine Polyketide Natural Products

Fungal Secondary Metabolites as Inhibitors of the Ubiquitin–Proteasome System

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